Orofacial pain: pharmacological treatments

The authors sought to review available literature relating to SSRI withdrawal syndromes

Temporomandibular disorders (TMD), which involve the masticatory muscles or the temporomandibular joint and burning mouth syndrome (BMS) are two of the more common causes of oro-facial. TMD affect around 10% of the adult population worldwide with BMS affecting between1 -15% of the population higher prevalence reported with age and in post-menopausal women

The aim was to carry out a health technology assessment (HTA) including a systematic review with NMA of randomised controlled trials to evaluate treatment efficacy, health economics and ethical aspects of pharmacological treatments in patients with chronic oro-facial pain.


Searches were conducted in the PubMed, Cochrane Library, Embase, National Health Service Economic Evaluation Database and HTA databases with no restrictions on language, patient age or duration of pain.

Randomised controlled trials(RCTs) in patents (≥18 years) with chronic (≥3 months) orofacial pain involving any type of pharmacological treatment (topical, local or general) compared with pharmacological treatment, other non-pharmacological treatment, placebo or no treatment involving more than 10 patients were considered. The primary outcome was pain intensity between 2weeks and 6 months, with quality of life as a secondary outcome.

3 review pairs independently assessed studies for inclusion with risk of bias being assessed independently by 4 review pairs.  The Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU) checklist was used. Data was abstracted independently by two reviewers. Studies that reported central and dispersion measures for pain intensity (VAS or NRS), both before and after treatment for individual interventions were eligible for network metal analysis (NMA) if the evaluated treatment could be linked to the network of evidence.


  • 57 studies were initially included,  16 studies had a high risk of bias and were excluded from the analysis
  • In the 41 remaining studies15 studies involving 790 patients for TMD-joint, 9 TMD-muscle studies involving 375 patients, and 17 BMS studies on 868 patients.
  • 8 studies on TMD-muscle and 5 on BMS were included in separate NMA.
  • The NMA showed that clonazepam and capsaicin reduced pain intensity in BMS, and the muscle relaxant cyclobenzaprine, for the TMD-muscle group.
  • A narrative synthesis suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments for TMD-joint pain.


The authors concluded: –

the narrative synthesis in the present review suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments of TMD-joint pain. The present NMA summarises the current evidence, albeit limited by the small number of studies that could be included, which reduces the generalisability of the results. Even with these limitations in mind, evidence has for the first time been provided with NMA that the muscle relaxant cyclobenzaprine has a positive treatment effect for TMD-muscle pain and that clonazepam and capsaicin are effective for BMS.


The main finding of this well-conducted review was that the NMA provided support for pharmacological treatment of patients with muscle-related TMD and BMS. However, the number of available studies is low and the quality of the available evidence is low.

A Cochrane review on treatments for BMS was published in 2016 (Dental Elf – 28th Nov 2016)  and concluded

Due to the limited number of clinical trials at low risk of bias, there is insufficient evidence to support or refute the use of any interventions in managing BMS. Further clinical trials, with improved methodology and standardised outcome sets are required in order to establish which treatments are effective.

 While this current review suggests that clonazepam and capsaicin are effective for BMS.


Primary paper

Häggman-Henrikson B, Alstergren P, Davidson T, Högestätt E, Östlund P,Tranaeus S, Vitols S, List T. Pharmacological treatment of orofacial pain -Health Technology Assessment including a systematic review with network meta-analysis. J Oral Rehabil. 2017 Jun 27. doi: 10.1111/joor.12539. [Epub ahead of print] Review. PubMed PMID: 28653747.

Other references

 Original review protocol on PROSPERO

Dental Elf – 28th Nov 2016

Burning mouth syndrome: insufficient evidence for effectiveness of current treatments

Dental Elf – TMD Blogs


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